RESUMEN
Functional interactions between neuroendocrine and immune systems are mediated by similar ligands and receptors, which establish a bi-directional communication that is relevant for homeostasis. We investigated herein the hypothalamus-pituitary-adrenal (HPA) axis in mice acutely infected by Trypanosoma cruzi, the causative agent of Chagas' disease. Parasites were seen in the adrenal gland, whereas T. cruzi specific PCR gene amplification product was found in both adrenal and pituitary glands of infected mice. Histological and immunohistochemical analyses of pituitary and adrenal glands of infected animals revealed several alterations including vascular stasis, upregulation of the extracellular matrix proteins fibronectin and laminin, as well as T cell and macrophage infiltration. Functionally, we detected a decrease in CRH and an increase in corticosterone contents, in hypothalamus and serum respectively. In contrast, we did not find significant changes in the amounts of ACTH in sera of infected animals, whereas the serum levels of the glucocorticoid-stimulating cytokine, IL-6 (interleukin-6), were increased as compared to controls. When we analyzed the effects of T. cruzi in ACTH-producing AtT-20 cell line, infected cultures presented lower levels of ACTH and pro-opiomelanocortin production when compared to controls. In these cells we observed a strong phosphorylation of STAT-3, together with an increased synthesis of IL-6, suppressor of cytokine signaling 3 (SOCS-3) and inhibitor of activated STAT-3 (PIAS-3), which could explain the partial blockage of ACTH production. In conclusion, our data reveal that the HPA axis is altered during acute T. cruzi infection, suggesting direct and indirect influences of the parasite in the endocrine homeostasis.
Asunto(s)
Enfermedad de Chagas/fisiopatología , Sistema Hipotálamo-Hipofisario/microbiología , Sistema Hipófiso-Suprarrenal/microbiología , Glándulas Suprarrenales/microbiología , Glándulas Suprarrenales/fisiología , Hormona Adrenocorticotrópica/análisis , Hormona Adrenocorticotrópica/metabolismo , Animales , Corticosterona/análisis , Corticosterona/metabolismo , Hormona Liberadora de Corticotropina/análisis , Hormona Liberadora de Corticotropina/metabolismo , Sistema Hipotálamo-Hipofisario/fisiología , Hipotálamo/microbiología , Hipotálamo/fisiología , Immunoblotting , Inmunohistoquímica , Interleucina-6/análisis , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Hipófisis/microbiología , Hipófisis/fisiología , Sistema Hipófiso-Suprarrenal/metabolismo , Proteínas Inhibidoras de STAT Activados/análisis , Proteínas Inhibidoras de STAT Activados/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT3/análisis , Factor de Transcripción STAT3/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/análisis , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Trypanosoma cruziRESUMEN
In previous studies we found an increase in body weight during the preclinical phase of disease in certain scrapie strain-mouse strain combinations. The effect was augmented by injection into the hypothalamus. In the present study, we found an increase in food consumption (compared to the normal mouse brain injection group) for both the 139A and ME7 scrapie groups, although only the ME7 group showed an increase in body weight. In a scrapie strain-mouse strain combination that showed an increase in body weight, the adrenal gland was the only organ that showed a significant increase in weight. The titer of scrapie in the adrenals was comparatively low. Adrenalectomy prevented the increase in body weight in two strains of mice injected with the ME7 scrapie strain. The results suggest that scrapie-induced obesity depends on an effect of scrapie on the hypothalamic-pituitary-adrenal axis.